TY - JOUR
AU - Renz, Alina
AU - Hohner, Mirjam
AU - Jami, Raphaël
AU - Breitenbach, Maximilian
AU - Josephs-Spaulding, Jonathan
AU - Dürrwald, Johanna
AU - Best, Lena
AU - Dulière, Victoria
AU - Mialon, Chloé
AU - Marinos, Georgios
AU - Leonidou, Nantia
AU - Cabreiro, Filipe
AU - Pellegrini, Marc
AU - Doerflinger, Marcel
AU - Rosa-Calatrava, Manuel
AU - Pizzorno, Andrés
AU - Dräger, Andreas
AU - Schindler, Michael
AU - Kaleta, Christoph
AU - Bader, Stefanie M.
PY - 2025
DA - May
TI - Metabolic modeling elucidates phenformin and atpenin A5 as broad-spectrum antiviral drugs against RNA viruses
JO - Communications Biology
VL - 8
DO - https://doi.org/10.1038/s42003-025-08148-y
AB - The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A virus with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.
PB - Springer Nature
UR - https://eprints.gla.ac.uk/356603/
KW - Coronavirus (COVID-19)
ER